This invention is directed to reagent packaging devices for storing one or more ingredients or reagents separate from one another in a single reagent package for subsequent mixing in the reagent package, and more particularly to a novel reagent package having a valve controlled opening that can be sealed independently of the valve. The invention is also directed to a reagent package having a novel liquid flow director system for directing substantially all liquid on a floor of the package into a liquid aspiration area and for preventing any minute glass particles that may surround the liquid aspiration area from entering the aspiration area.
Automated sample analysis systems as disclosed in U.S. Pat. Nos. 5,268,167 and 5,399,497 can perform a variety of different tests on a test subject, such as a serum sample, in a relatively short period of time. Generally the serum sample is separated into a predetermined number of segregated portions and a different test is usually performed on each segregated portion of the serum sample. It is thus common practice to divide the serum sample into a series of separate isolated sample segments that correspond to each separate test. The isolated sample segments are enabled to co-act with specific reagents to produce an analyzable reaction that forms the basis for a test result.
Different reagents will produce different test results on respective sample segments and the compendium of the separate test results provide a body of information or data relating to the characteristics of the serum sample.
As used herein, the term reagent is intended to refer to a single reagent, a mixture of two or more reagents and/or a mixture of reagent with a reconstituting liquid.
Reagents for sample analysis systems are preferably used in liquid form to permit allotment of a precise predetermined amount of reagent to each sample segment and to help ensure that the reaction between the reagent and the serum sample is uniform. Generally, the reagent is diluted to a desired concentration before it is permitted to co-act with a serum sample.
It is well known that some reagents used in sample analysis systems have a limited shelf life especially if produced as a solution of one or more reagent components. Therefore, optimum test results between a reagent and a serum sample are usually obtained if the reagent is dissolved or diluted shortly before being used for test purposes.
Since the shelf life of a reagent in dry form is usually longer than the shelf life of the reagent in a liquid condition it is common practice to maintain a reagent in dry condition in a reagent mixing package. In some instances, the mixing package is arranged to hold in segregated condition a dry reagent component and a liquid reconstituting component. When use of the reagent is desired, the components are intermixed within the package.
One known reagent package such as shown in U.S. Pat. No. 4,515,753 includes a reagent in lyophilized powder form in a first breakable capsule and a reconstituting liquid for the reagent in a second breakable capsule. The capsules are broken by compressing the package to release the contents of each capsule for mixing within the package. An outlet port in the package permits outside access to the mixed ingredients. Although this reagent package provides a freshly mixed reagent for immediate use in a sample analysis system, it is difficult to seal the package once the ingredients have been mixed. This package also does not permit long term preservation of liquid that is openly contained in the package and therefore the reconstituting liquid must be maintained in a capsule.
It is thus desirable to provide a reagent package that can be sealed when it is in storage awaiting use and also provide for sealing of the package after the package contents are mixed for use.
Generally, the liquid mixture contained in the reagent package is one of the most expensive consumable constituents of a sample analysis system. For example the contents of an individual reagent package can cost approximately $600 to $1,000 for approximately 20 to 25 milliliters of mixed reagent.
It is thus beneficial to be able to conveniently withdraw substantially all of the liquid reagent that is mixed in a reagent package. It is also desirable that such withdrawal of reagent be free of any fragmentary glass particles that result from breakage of a glass ampoule in the package after the ampoule is broken to release a constituent of the reagent mixture.
It is also desirable to provide a reagent package for one or more reagent components wherein the package has a valve controlled opening that can also be sealed independently of the valve, and which package permits use of substantially all of the mixed ingredients in the reagent package without contamination from glass particles after an ampoule is broken in the reagent package;
Among the several objects of the invention may be noted the provision of a novel reagent package having a valve controlled opening, a novel reagent package having a valve controlled opening wherein the valve can be locked in a closed position with a locking clip to provide a substantially leak-tight seal, a novel reagent package having a valve controlled opening wherein the valve in a movable condition, without the locking clip provides an evaporation barrier for liquid contained in the package when the valve is in a closed position, a novel reagent package having a valve controlled opening wherein the valve can be rendered movable with respect to the container opening to optionally select open and closed positions of the reagent package, a novel reagent package that can accommodate a breakable ampoule with one reagent and an openly stored reconstituting liquid, a novel reagent package having a valve controlled opening wherein the valve can be locked in a closed position to provide a substantially leak tight seal that permits long term storage of a liquid reagent, a novel reagent package with a breakable ampoule and a filter screen that is structured to resist damage from broken glass, a novel reagent package which can be deformed to break a frangible ampoule inside the package without damaging the package and without damaging a valve provided on the package, a novel reagent package having two separate non-communicable chambers to constitute a dual reagent package, a novel reagent package that provides valve controlled access to substantially all liquid reagent in the package, a novel reagent package that accommodates a breakable ampoule and permits aspiration of reagent from the broken ampoule without the glass particles, and a novel method of providing controlled access to a reagent in a package.
Further objects include the provision of a novel reagent package having a valve controlled opening that can be sealed independently of the valve to provide a tighter seal than the valve provides, a novel reagent package with flow channels formed in the floor of the package that are directed to a liquid aspiration area, and a novel means for preventing any minute fragmentary particles that may surround the liquid aspiration are from entering the liquid aspiration area. Other objects and features of the invention will be in part apparent and in part pointed out hereinafter.
In accordance with the present invention, the reagent package includes a container having an inside chamber and a restrictable opening to the chamber. A valve is positioned on the container to control the opening. The valve has a valve closed position to close off and seal the opening and a valve open position to permit access to the container chamber through the container opening. Preferably the valve is a rocker valve which is pivotable about a pivot axis that is spaced above the container opening.
In a preferred embodiment of the invention the reagent package is a dual package and includes two separate chambers that are non communicable with each other. Each chamber has a separate opening controlled by a separate rocker valve. The rocker valves are identical and have pivots that are cantilevered at the end of pivot support arms to permit deflection between the valve face and the valve pivots.
When the reagent package is in a valve closed position reagent materials inside the container cannot be accessed. Also when the reagent package is in a valve closed position a locking clip can be placed on the package to further secure the valves against the container opening thereby enhancing the valve seal. The locking clip enables the ingredients of the reagent package to be stored without degradation for approximately two years under refrigeration.
In one embodiment of the invention the reagent package includes a hollow filter screen member in each chamber and a breakable glass ampoule in each chamber. The glass ampoule contains one reagent ingredient and is preferably in a dry lyophilized condition. The internal chamber space outside the glass ampoule can accommodate a reconstituting liquid. When it is desired to use the ingredients of the reagent package, a compression force is applied to the outside wall of the reagent package proximate the glass ampoule to crush the ampoule. The contents of the ampoule are thus released and can mix inside the package chamber with the reconstituting liquid. If desired, the ampoule can contain a liquid ingredient.
The reagent package also includes a well portion that defines the lowest point in the package. The well portion receives a bottom portion of the filter screen member and also receives through the screen of the filter member the mixed ingredients of the reagent package. The screen member filters out any broken glass from the crushed ampoule. The mixed ingredients of the reagent package are aspirated through the hollow space of the filter member. As the chamber ingredients are depleted during aspiration of reagent the unused reagent tends to flow into the bottom of the screen member in the filter well where it can be easily aspirated thus minimizing or eliminating any waste of reagent material.
The invention also includes a method of providing controlled access to a reagent. A closed container is provided with a valve controlled opening to maintain the container in a sealed condition when the valve is in a closed position and to provide access to the container when the valve is in an open position. The method further includes arranging the valve as a rocker valve at the opening of the container such that the valve is pivotable about an axis that is spaced from the container opening. The rocker valve can thus be pivoted from the valve open position to the valve closed position and vice versa. The rocker valve is provided with a valve face having opposite ends. Pivot means for the rocker valve connect to only one end of the valve face in cantilever arrangement. The cantilever arrangement permits the valve face to be deflectable from the pivot axis and permits pressure sealing of the valve face against the opening in the container.
In another embodiment of the invention the floor portion of the reagent package is formed with channels directed toward the filter well. The channels have a lowermost end portion at the periphery of the filter well. Downwardly directed micro-slits are formed in the bottom portion of the filter and also in the peripheral wall of the filter well. The micro-slits in the filter well align with the channels formed in the floor of the reagent package. The micro-slits formed in the bottom portion of the filter member have an upper end that is communicable with the fluid chamber surrounding the filter member and a lower end that communicates with the space in the filter well below the filter member.
The bottom portion of the filter member and the peripheral wall of the filter well are of complimentary shape. The bottom portion of the filter also includes a deflectable circumferential toe flange that contacts the peripheral wall of the filter well when the filter is installed in the filter well.
The bottom portion of the filter member can thus make surface contact with the peripheral wall of the filter well due to the complimentary shape of the bottom portion of the filter member and the peripheral wall of the well. The bottom portion of the filter member can also make circumferential line contact with the peripheral wall of the filter well where the circumferential toe portion of the filter contacts the wall of the filter well.
Under this arrangement liquid that is on the floor of the reagent package can drain into the filter well through the floor channels and through the micro-slits at the bottom portion of the filter member and in the wall of the filter well. Fluid on the floor of the reagent package may also seep between the surface contact area of the filter and the filter well and between the circumferential line contact area between the bottom portion of the filter member and the wall of the filter well.
However, any fragmentary solid glass material in the mixing chamber of the reagent package due to breakage of the glass ampoule is prevented from entering the filter well because of the surface contact between the filter and the filter well and because of the circumferential line contact between the filter member and the filter well wall.
The valve of the reagent package which is pivotable on the package, has a cover-like closure or sealing portion and an open portion. The valve is movable to a closed position wherein the sealing portion closes the container opening. The valve is also movable to an open position wherein the open portion of the valve aligns with the container opening to expose the container opening.
In still another embodiment of the invention a plug member has a plug portion engagable in the container opening when the valve is in the open position. The plug member plugs the container opening when the reagent package is being stored or shipped and is not yet ready for use. The engagement of the plug member in the container opening through the open portion of the valve prevents the valve from moving.
When the reagent package is ready for use the plug member is removed from the container opening thereby permitting movement of the valve. The valve can then be moved to the closed position wherein the sealing portion of the valve covers the container opening. The reagent package can then be prepared for internal ampoule breakage and reagent mixing while the broken ampoule remains in place in the reagent package.
The invention accordingly comprises the constructions and method hereinafter described, the scope of the invention being indicated in the claims.